ORIGINAL ARTICLE Oviduct as a sensor of embryo quality: deciphering the extracellular vesicle (EV)-mediated embryo-maternal dialogue Keerthie Dissanayake 1,2,3 & Monika Nõmm 3 & Freddy Lättekivi 1 & James Ord 1 & Yosra Ressaissi 1,4 & Kasun Godakumara 1,3 & Qurat Ul Ain Reshi 1,3 & Janeli Viil 1 & Kersti Jääger 5 & Agne Velthut-Meikas 6 & Andres Salumets 3,5,7,8 & Ülle Jaakma 3 & Alireza Fazeli 1,9,3 Received: 1 October 2020 /Revised: 7 December 2020 /Accepted: 18 January 2021 # The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021 Abstract Embryo-derived extracellular vesicles (EVs) may play a role in mediating the embryo-maternal dialogue at the oviduct, poten- tially carrying signals reflecting embryo quality. We investigated the effects of bovine embryo-derived EVs on the gene expression of bovine oviductal epithelial cells (BOECs), and whether these effects are dependent on embryo quality. Presumptive zygotes were cultured individually in vitro in culture medium droplets until day 8 while their development was assessed at day 2, 5 and 8. Conditioned medium samples were collected at day 5 and pooled based on embryo development (good quality embryo media and degenerating embryo media). EVs were isolated from conditioned media by size exclusion chroma- tography and supplemented to primary BOEC monolayer cultures to evaluate the effects of embryo-derived EVs on gene expression profile of BOEC. Gene expression was quantified by RNA-seq and RT-qPCR. A total of 7 upregulated and 18 downregulated genes were detected in the BOECs supplemented with good quality embryo-derived EV compared to the control. The upregulated genes included interferon-τ-induced genes, such as OAS1Y, MX1 and ISG15, which have previously been reported as upregulated in the oviductal epithelial cells in the presence of embryos. Of the upregulated genes, OAS1Y and MX1 were validated with RT-qPCR. In contrast, only one differentially expressed gene was detected in BOECs in response to degenerating embryo-derived EVs, suggesting that oviductal responses are dependent on embryo quality. Our results support the hypothesis that embryo-derived EVs are involved in embryo-maternal communication at the oviduct and the oviductal response is dependant on the embryo quality. Key messages • Extracellular vesicles (EVs) released by individually cultured pre-implantation bovine embryos can alter the gene expression of primary oviductal epithelial cells. • The oviductal response, in terms of gene expression, to the bovine embryo-derived EVs varied depending on the embryo quality. • In vivo, the oviduct may have the ability to sense the quality of the pre-implantation embryos. • The observed effect of embryo-derived EVs on oviductal epithelial cells could serve as a non-invasive method of evaluating the embryo quality. Keywords Bovine embryo . Embryo-maternal communication . Extracellular vesicles . Oviduct * Alireza Fazeli alireza.fazeli@ut.ee 1 Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, 14B Ravila, 50411 Tartu, Estonia 2 Department of Anatomy, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka 3 Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, Estonia 4 Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy 5 Competence Centre on Health Technologies, Tartu, Estonia 6 Department of Chemistry and Biotechnology, School of Science, Tallinn University of Technology, Tallinn, Estonia 7 Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia 8 Institute of Genomics, University of Tartu, Tartu, Estonia 9 Academic Unit of Reproductive and Developmental Medicine, Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK https://doi.org/10.1007/s00109-021-02042-w / Published online: 29 January 2021 Journal of Molecular Medicine (2021) 99:685–697